Skip to main content

Advertisement

SpringerLink
Log in

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Tibial compression can increase murine bone mass. However, loading protocols and mouse strains differ between studies, which may contribute to conflicting results. We hypothesized that bone accrual is influenced more by loading history than by mouse strain or animal handling. The right tibiae of 4-month-old C57BL/6 and BALB/c mice were subjected to axial compression (10 N, 3 days/week, 6 weeks). Left tibiae served as contralateral controls to calculate relative changes: (loaded − control)/control. The WashU protocol applied 60 cycles/day, at 2 Hz, with a 10-s rest-insertion between cycles; the Cornell/HSS protocol applied 1,200 cycles/day, at 6.7 Hz, with a 0.1-s rest-insertion. Because sham loading, sedation, and transportation did not affect tibial morphology, unhandled mice served as age-matched controls (AC). Both loading protocols were anabolic for cortical bone, but Cornell/HSS loading elicited a more rapid response that was greater than WashU loading by 13 %. By 6 weeks, cortical bone volume of each loading group was greater than of AC (average + 16 %) and not different from each other. Ultimate displacement and energy to fracture were greater in tibiae loaded by either protocol, and ultimate force was greater with Cornell/HSS loading. At 6 weeks, independent of mouse strain, the WashU protocol produced minimal trabecular bone and the trabecular bone volume fraction of Cornell/HSS tibiae was greater than that of AC by 65 % and that of WashU by 44 %. We concluded that tibial adaptation to loading was more influenced by waveform than mouse strain or animal handling and therefore may have targeted similar osteogenic mechanisms in C57BL/6 and BALB/c mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Robling AG, Burr DB, Turner CH (2001) Skeletal loading in animals. J Musculoskelet Neuronal Interact 1:249–262

    PubMed  CAS  Google Scholar 

  2. De Souza RL, Matsuura M, Eckstein F, Rawlinson SC, Lanyon LE, Pitsillides AA (2005) Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone 37:810–818

    Article  PubMed  Google Scholar 

  3. Fritton JC, Myers ER, Wright TM, van der Meulen MC (2005) Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone 36:1030–1038

    Article  PubMed  CAS  Google Scholar 

  4. Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455–498

    Article  PubMed  CAS  Google Scholar 

  5. Turner CH, Owan I, Takano Y (1995) Mechanotransduction in bone: role of strain rate. Am J Physiol Endocrinol Metab 269:E438–E442

    CAS  Google Scholar 

  6. Warden SJ, Turner CH (2004) Mechanotransduction in the cortical bone is most efficient at loading frequencies of 5–10 Hz. Bone 34:261–270

    Article  PubMed  CAS  Google Scholar 

  7. Rubin CT, Lanyon LE (1984) Regulation of bone formation by applied dynamic loads. J Bone Joint Surg Am 66:397–402

    PubMed  CAS  Google Scholar 

  8. Srinivasan S, Ausk BJ, Poliachik SL, Warner SE, Richardson TS, Gross TS (2007) Rest-inserted loading rapidly amplifies the response of bone to small increases in strain and load cycles. J Appl Physiol 102:1945–1952

    Article  PubMed  Google Scholar 

  9. Srinivasan S, Weimer DA, Agans SC, Bain SD, Gross TS (2002) Low-magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle. J Bone Miner Res 17:1613–1620

    Article  PubMed  Google Scholar 

  10. LaMothe JM, Zernicke RF (2004) Rest insertion combined with high-frequency loading enhances osteogenesis. J Appl Physiol 96:1788–1793

    Article  PubMed  Google Scholar 

  11. Brodt MD, Silva MJ (2010) Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compression. J Bone Miner Res 25:2006–2015

    Article  PubMed  Google Scholar 

  12. Silva MJ, Brodt MD, Lynch MA, Stephens AL, Wood DJ, Civitelli R (2012) Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice. PLoS One 7:e34980

    Article  PubMed  CAS  Google Scholar 

  13. Lynch ME, Main RP, Xu Q, Walsh DJ, Schaffler MB, Wright TM et al (2010) Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. J Appl Physiol 109:685–691

    Article  PubMed  Google Scholar 

  14. Lynch ME, Main RP, Xu Q, Schmicker TL, Schaffler MB, Wright TM et al (2011) Tibial compression is anabolic in the adult mouse skeleton despite reduced responsiveness with aging. Bone 49:439–446

    Article  PubMed  Google Scholar 

  15. Judex S, Donahue LR, Rubin C (2002) Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J 16:1280–1282

    PubMed  CAS  Google Scholar 

  16. Akhter MP, Cullen DM, Pedersen EA, Kimmel DB, Recker RR (1998) Bone response to in vivo mechanical loading in two breeds of mice. Calcif Tissue Int 63:442–449

    Article  PubMed  CAS  Google Scholar 

  17. Poliachik SL, Threet D, Srinivasan S, Gross TS (2008) 32 wk old C3H/HeJ mice actively respond to mechanical loading. Bone 42:653–659

    Article  PubMed  Google Scholar 

  18. Christiansen BA, Kotiya AA, Silva MJ (2009) Constrained tibial vibration does not produce an anabolic bone response in adult mice. Bone 45:750–759

    Article  PubMed  Google Scholar 

  19. Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK (2007) Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone 41:505–515

    Article  PubMed  Google Scholar 

  20. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486

    Article  PubMed  Google Scholar 

  21. Buie HR, Moore CP, Boyd SK (2008) Postpubertal architectural developmental patterns differ between the L3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res 23:2048–2059

    Article  PubMed  Google Scholar 

  22. Mori T, Okimoto N, Sakai A, Okazaki Y, Nakura N, Notomi T et al (2003) Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice. J Bone Miner Res 18:2002–2009

    Article  PubMed  Google Scholar 

  23. Iwamoto J, Yeh JK, Aloia JF (1999) Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat. Bone 24:163–169

    Article  PubMed  CAS  Google Scholar 

  24. Robling AG, Burr DB, Turner CH (2000) Partitioning a daily mechanical stimulus into discrete loading bouts improves the osteogenic response to loading. J Bone Miner Res 15:1596–1602

    Article  PubMed  CAS  Google Scholar 

  25. Ko FC, Dragomir C, Plumb DA, Goldring SR, Wright TM, Goldring MB et al (2013) In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. Arthritis Rheum. doi:10.1002/art.37906

    Google Scholar 

  26. Stadelmann VA, Bonnet N, Pioletti DP (2011) Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia. Clin Biomech (Bristol, Avon) 26:101–105

    Article  CAS  Google Scholar 

  27. Kodama Y, Umemura Y, Nagasawa S, Beamer WG, Donahue LR, Rosen CR et al (2000) Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6 J mice but not in C3H/Hej mice. Calcif Tissue Int 66:298–306

    Article  PubMed  CAS  Google Scholar 

  28. Umemura Y, Ishiko T, Yamauchi T, Kurono M, Mashiko S (1997) Five jumps per day increase bone mass and breaking force in rats. J Bone Miner Res 12:1480–1485

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the National Institutes of Health (R01 AR047867, P30 AR057235).

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Washington University, 425 S Euclid Ave., St. Louis, MO, 63110, USA

    Nilsson Holguin, Michael D. Brodt, Michelle E. Sanchez, Akhilesh A. Kotiya & Matthew J. Silva

  2. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

    Matthew J. Silva

Authors
  1. Nilsson Holguin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael D. Brodt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michelle E. Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akhilesh A. Kotiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew J. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nilsson Holguin.

Additional information

M.J. Silva has consultant/advisory role to and has received funding from Merck that is unrelated to this manuscript. All other authors have stated that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holguin, N., Brodt, M.D., Sanchez, M.E. et al. Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice. Calcif Tissue Int 93, 211–221 (2013). https://doi.org/10.1007/s00223-013-9744-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-013-9744-4

Keywords

Search

Navigation